| 【Background】In the practice of forensic medicine,the diagnosis of the underlying disease suffered by the deceased is mainly based on morphological methods.However,some hereditary heart diseases,such as arrhythmias and cardiomyopathies,may lack clear or specific morphologic pathologic changes.Therefore,some decedents are often defined as Unexplained Sudden Death(USD)or Unexplained Sudden Cardiac Death(USCD)because of the absence of significant morphologic changes in the pathologic autopsy or the presence of only indeterminate nonspecific changes.Studies have shown that these USD decedents had underlying genetic arrhythmias or cardiomyopathies.Molecular autopsy or genetic testing can improve the accuracy of USCD diagnosis.Previous studies on molecular autopsy have focused on cardiac dysfunctional diseases such as arrhythmias.However,the authors believe that molecular autopsy also has promising applications in diseases that have previously been diagnosed morphologically.For example,although myocardial morphologic changes exist to varying degrees in cardiomyopathies,some morphologic changes are not very specific and often do not show obvious characteristic pathomorphologic changes,or because morphologic testing is a way that relies more on the subjective judgment of the pathologic examiner,there is a lack of more objective evidence for the diagnosis of cardiomyopathies,which makes the diagnosis of cardiomyopathies subject to a certain amount of erroneous subjective bias.It should also be added and that genetic diagnosis has limitations,for example,because of the large number of variant information,only a few diseases can be diagnosed by clear genetic mutations alone,and for most polygenic-related diseases,the judgment criteria for genetic test results are complex and prone to false positives and other misjudgments when used alone,and should be combined with clinical symptoms or other ancillary test results.Therefore,we believe that using autopsy and histopathological findings as phenotypic auxiliary information for the judgment of gene test results will effectively improve the accuracy of analysis and compensate for the lack of clinical medical records and other information in patients with sudden death.The joint application of molecular autopsy and pathological anatomy is more in line with the actual situation and needs of forensic identification.【Objective】(1)To explore the diagnostic strategy of the combination of molecular anatomy and pathological anatomy in the diagnosis of cardiomyopathy in forensic medicine.(2)Application of molecular anatomy in forensic diagnosis of cardiomyopathy.【Methods】(1)Collection of samples: the organs,tissues and blood samples of the dead with suspected cardiomyopathy were collected through pathological anatomy.(2)Molecular anatomy: genomic DNA extraction,whole exome sequencing,bioinformatics analysis of pathogenic / possible pathogenic variation sites.(3)The results of molecular anatomy and pathological anatomy were combined to diagnose cardiomyopathy.【Results】(1)Three cases of suspected sudden cardiac death were diagnosed by a combined molecular autopsy and pathologic anatomy diagnostic strategy,with a combined diagnosis rate of 37.5%(6/16).(2)Molecular autopsy revealed 8 pathogenic/probably pathogenic variants in 6 deceased individuals(6/16,37.5%).(3)Diagnosis of cardiomyopathy was confirmed in 3 decedents(3/16,19%)by a combined molecular autopsy and pathological autopsy strategy.(4)Two de novo variant loci were identified: the INDEL variant of the TTN gene(2:178560793:C:CT),and a INDEL of the ALMS1 gene(2:73675333:CA:C).【Conclusion】This study combines molecular anatomy and pathological anatomy,puts forward a diagnostic idea of combining molecular anatomy and pathological anatomy,and applies it to practical cases.Through the joint diagnosis of 16 death cases,it is found that the combination of molecular anatomy and pathological anatomy can improve the accuracy of diagnosis and provide more clues and evidence for the diagnosis of forensic cardiomyopathy. |
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